Phthalocyanines are a group of photoactive compounds that are somewhat structurally similar (i.e., have nitrogen containing ring structure) to the porphyrin family. Phthalocyanines are azaporphyrins consisting of four benzoindole nuclei connected by nitrogen bridges in a 16-membered ring of alternating carbon and nitrogen atoms around a central metal atom (i.e., C32H16N8M) which form stable chelates with metal cations. In these compounds, the ring center is occupied by a metal ion (such as a diamagnetic or a paramagnetic ion) that may, depending on the ion, carry one or more ligands. In addition, the ring periphery may be either unsubstituted or substituted.
Owing to their high stability and unique physicochemical properties, phthalocyanines and related macrocycles have found widespread applications in various disciplines (Phthalocyanines-Properties and Applications; Leznoff and Lever, Eds.; VCH: New York, 1989, Vol. 1; 1993, Vols. 2 and 3; 1996, Vol. 4.) Numerous studies have been carried out to modify these tetrapyrrole derivatives with the goal of modifying their properties and optimizing their performance as advanced materials. For some applications, such as photodynamic therapy, photoinactivation of viruses in stored blood products, and the photooxidation of mercaptans in petroleum distillates, it is desirable that the macrocycles are free of molecular aggregation (Bonnet, Chem. Soc. Rev. 1995, 19; Milgrom et al. Chem. Br. 1998 (May), 45; Rywiken, S. et al. Photochem. Photobiol. 1994, 60:165; Abe, H. et al. Photochem. Photobiol. 1995, 61:402; Allen, C. M. et al. Photochem. Photobiol. 1995, 62:184; Iliev, V. et al. J. Chem. Soc. Catal. A. Chem. 1995, 103:147; Kimura et al. J. Porphyrins Phthalocyanines, 1997, 1:309).
Molecular aggregation, a common phenomenon of this family of compounds, drastically decreases the compounds"" luminescence quantum yield, which results in decreased photosensitizing efficiency (Tai, S. et al. J. Chem. Soc. Perkin Trans. 2 1991, 1275; Schutte, W. et al. J. Phys. Chem. 1993, 97:6069; Spikes, D. J. Photochem. Photobiol. 1986, 43:691; Vacus, J. et al Adv. Mater. 1995, 7:797; Dharni, S et al. J. Photochem. Photobiol A: Chem. 1996, 100:77; Howe, L. et al. J Phys. Chem. A, 1997, 101:3207). Increased water solubility of phthalocyanines has been shown to decrease their aggregation tendencies (Schelly, Z. A. et al. J. Phys. Chem. 1970, 74:3040; Yang, Y. C. et al. Inorg. Chem. 1985, 24:1765). Hydrophilic and non-aggregating phthalocyanines are potentially useful materials, but the study of these phthalocyanines is still in its infancy (Kimura, M. et al. Chem. Commun. 1997, 1215).
The invention pertains, at least in part, to phthalocyanine compounds of formula 
wherein X1-8 are each halogen and R1-8 are each independently halogen or an anti-stacking moiety.
The invention also includes phthalocyanine compounds of formula II:
[MxLySz]Cwxe2x80x83xe2x80x83(II)
wherein M is a metal, L is an anion of a phthalocyanine compound of formula I as defined above, S is an organic or inorganic ligand, C is a counterion, x and y are numbers greater than zero, and z and w are numbers zero or greater. In preferred embodiments, M is a metal cation.
In one embodiment, R1-8 are not all halogen. In another embodiment, each of X1-8 is fluorine. In another embodiment, the anti-stacking moieties are inert to activated oxygen and may be selected such that the phthalocyanine compound is soluble in water. In yet another embodiment, the anti-stacking moieties are branched alkyl and are, advantageously, perhalogenated. In one embodiment, the anti-stacking moiety is perfluorinated branched alkyl. In another embodiment, M is diamagnetic.
The invention also pertains to a pharmaceutical composition, comprising a pharmaceutically acceptable carrier and an effective amount of a phthalocyanine compound of formula II, as described above, and pharmaceutically acceptable salts thereof. In one embodiment, the pharmaceutical composition is suitable for the treatment of a condition in a patient. In a preferred embodiment, the composition is suitable for treating cancer in a patient, e.g., by using photodynamic therapy.
In yet another embodiment, the invention features a method for treating a condition in a patient, by administering to the patient an effective amount of a phthalocyanine compound of formula II, as described above. In one embodiment, the method comprises exposing the patient to light to achieve photodynamic therapy. Preferably, the condition is cancer and the effective amount is effective to treat cancer.
The invention also includes a method of photoinactivating viruses in blood, by contacting the blood with an effective amount of a phthalocyanine compound of formula II, as described above. The invention also pertains to a dye and a composition for organometallic catalysis each comprising at least one phthalocyanine compound of formula II.